A Novel LINS1 Truncating Mutation in Autosomal Recessive Nonsyndromic Intellectual Disability

Babylakshmi Muthusamy, Anikha Bellad, Pramada Prasad, Aravind K. Bandari, G. Bhuvanalakshmi, R. M. Kiragasur, Satish Chandra Girimaji, Akhilesh Pandey

Research output: Contribution to journalArticle

Abstract

The large majority of cases with intellectual disability are syndromic (i.e. occur with other well-defined clinical phenotypes) and have been studied extensively. Autosomal recessive nonsyndromic intellectual disability is a group of genetically heterogeneous disorders for which a number of potentially causative genes have been identified although the molecular basis of most of them remains unexplored. Here, we report the clinical characteristics and genetic findings of a family with two male siblings affected with autosomal recessive nonsyndromic intellectual disability. Whole exome sequencing was carried out on two affected male siblings and unaffected parents. A potentially pathogenic variant identified in this study was confirmed by Sanger sequencing to be inherited in an autosomal recessive fashion. We identified a novel nonsense mutation (p.Gln368Ter) in the LINS1 gene which leads to loss of 389 amino acids in the C-terminus of the encoded protein. The truncation mutation causes a complete loss of LINES_C domain along with loss of three known phosphorylation sites and a known ubiquitylation site in addition to other evolutionarily conserved regions of LINS1. LINS1 has been reported to cause MRT27 (mental retardation, autosomal recessive 27), a rare autosomal recessive nonsyndromic intellectual disability, with limited characterization of the phenotype. Identification of a potentially pathogenic truncating mutation in LINS1 in two profoundly intellectually impaired patients also confirms its role in cognition.

Original languageEnglish (US)
Article number354
JournalFrontiers in Psychiatry
Volume11
DOIs
StatePublished - May 18 2020

Keywords

  • Embryogenesis
  • WNT signalling
  • autosomal recessive
  • genetic disorders
  • truncating mutation

ASJC Scopus subject areas

  • Psychiatry and Mental health

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  • Cite this

    Muthusamy, B., Bellad, A., Prasad, P., Bandari, A. K., Bhuvanalakshmi, G., Kiragasur, R. M., Girimaji, S. C., & Pandey, A. (2020). A Novel LINS1 Truncating Mutation in Autosomal Recessive Nonsyndromic Intellectual Disability. Frontiers in Psychiatry, 11, [354]. https://doi.org/10.3389/fpsyt.2020.00354